Medicament delivery device

ABSTRACT

The present disclosure relates to a medicament delivery device includes a housing configured to receive a cartridge containing a medicament, an injection needle having a proximal end and a distal end, an injection needle holder to which the injection needle is fixed, the injection needle holder being moveable relative to the housing between a rest position and a use position, and an injection needle cap detachably connected to the injection needle holder and enclosing the proximal end of the injection needle. The medicament delivery device is configured such that pushing the injection needle cap towards the cartridge causes the injection needle holder to move from the rest position in which the distal end of the injection needle is spaced from the cartridge towards the use position in which the distal end of the injection needle can engage the cartridge.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a divisional application of U.S. patentapplication Ser. No. 15/779,055, filed on May 24, 2018, which is thenational stage entry of International Patent Application No.PCT/EP2016/078261, filed on Nov. 21, 2016, and claims priority toApplication No. EP 15196692.6, filed in on Nov. 27, 2015, thedisclosures of which are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure relates to a device for delivery of medicament toa patient.

BACKGROUND

Medicament injection devices such as auto-injectors are a common type ofmedicament delivery devices designed to deliver a medicament byinjection. This type of devices are designed to be easy to use andintended for self-administration by patients, or administration bypersons having no formal medical training.

Some medicament injection devices operate with a cartridge-basedinjection system. This type of injection devices is typically providedwith a separate cartridge pre-filled with medicament and a separateneedle sealed in a sterilised packaging. Before the injection, thepatient has to place the cartridge in a cartridge holder located withinthe housing of the device, unseal the packaging containing the needle,and position the needle in the housing of the device. Therefore, thepatient has to perform several steps before being able to carry out theinjection, which can be time-consuming and uncomfortable, in particularfor patients of impaired physical ability.

Medicament injection devices operating with a syringe-based injectionsystem also exist. This type of injection devices typically comprises asyringe pre-filled with medicament having a needle already fixed to thebody of the syringe. Before the injection, the patient places thesyringe in the housing of the device. During the injection, the wholesyringe is moved forward to penetrate the patient's skin. The syringesused with this latter type of devices are often stored during arelatively long time before being effectively used for injection. Oneproblem is that, during this time of storage, the medicament remains incontact with the needle of the syringe and a clogging of the needle bythe medicament may occur. This effect often occurs in combination withmonoclonal antibodies, such as PCSK-9. This clogging can lead to anincrease in injection time or stalling of the injection.

At least in certain embodiments, the present disclosure sets out toovercome or ameliorate at least some of the problems mentioned above. Inparticular, the present disclosure sets out to provide a device fordelivery of medicament of convenient and efficient use.

SUMMARY

Aspects of the present disclosure relate to a device for delivery ofmedicament to a patient.

According to a further aspect of the present disclosure, there isprovided a method comprising:

-   -   pushing an injection needle cap of a medicament delivery device        toward a cartridge such that a holder for an injection needle is        moved distally from a rest position and such that a distal end        of an injection needle engages the cartridge; and    -   pulling the injection needle cap away from the cartridge to        expose a proximal end of the injection needle of the medicament        delivery device for injection.

Pushing the injection needle cap towards the cartridge may comprisecausing the holder for an injection needle to move from the restposition in which the distal end of the injection needle may be spacedfrom the cartridge towards a use position in which the distal end of theinjection needle may engage the cartridge.

Pushing the injection needle cap toward the cartridge may comprisecausing a plurality of arms of the holder to move away from each othersuch that a breakable material connecting the plurality of arms maybreak.

The breakable material may break along a frangible line which may beprovided in the breakable material.

The breakable material may comprise a foil.

In the rest position, before pushing the injection needle cap toward thecartridge, the distal end of the injection needle may be sealed by theplurality of arms, the breakable material, and the cartridge.

Pushing the injection needle cap toward the cartridge may comprisecausing a plurality of arms of the holder to slide along the cartridge.The plurality of arms may be in contact with the cartridge as they slidealong the cartridge.

In the rest position, before pushing the injection needle cap toward thecartridge, the plurality of arms may project from the holder and mayextend around the distal end of the injection needle.

The plurality of arms may comprise a first arm and a second arm, whereinthe first and second arms may face each other and may extend around thedistal end of the injection needle.

The plurality of arms may comprise a flexible material.

Pushing the injection needle cap toward the cartridge may comprisecausing a locking mechanism of the medicament delivery device to preventthe holder from moving back toward the rest position.

The locking mechanism may allow the holder to move in a first axialdirection which may be towards the cartridge and may be to a useposition, it may prevent the holder from moving in a second axialdirection which may be opposed to the first axial direction once theholder has reached the use position.

The locking mechanism may comprise a first locking element which may beprovided on a housing of the medicament delivery device and a secondlocking element which may be provided on the holder, wherein, when theholder is in the use position, the first locking element and the secondlocking element may cooperate which may prevent the holder from movingback towards the rest position.

The locking mechanism may comprise a first locking element which may beprovided on a housing of a medicament delivery device and a secondlocking element which may be provided on the holder, wherein pushing theinjection needle cap toward the cartridge may comprise causing thesecond locking element to move beyond the first locking element and mayabut against the second locking element, which may prevent the holderfrom moving back towards the rest position.

The locking mechanism may comprise at least one projection which may beprovided on the holder and at least one clip which may be provided on ahousing of a medicament delivery device, wherein pushing the injectionneedle cap toward the cartridge may comprise causing the projection tomove beyond the clip and may abut against the clip, which may preventthe holder from moving back towards the rest position.

In the rest position, the holder may be prevented from being removedfrom a housing of the medicament delivery device by a retainingmechanism.

Before pushing the injection needle cap toward the cartridge, aretaining element which may be provided on at least one of a pluralityof arms of the holder may cooperate with the cartridge which may preventthe holder from being removed from a housing of the medicament deliverydevice.

Pushing the injection needle cap towards the cartridge may comprisecausing a fastening element which may be provided on at least one of aplurality of arms of the holder to cooperate with the cartridge, whichmay prevent the holder from moving towards the rest position.

Pushing the injection needle cap towards the cartridge may comprisecausing a fastening element which may be provided on at least one of aplurality of arms of the holder to cooperate with the cartridge, suchthat the holder may be fixed relative to the cartridge.

Pulling the injection needle cap away from the cartridge may comprisedetaching the injection needle cap from the holder which may causedisengagement of an outer sleeve of the medicament delivery device froma housing of the medicament delivery device.

According to a further aspect of the present disclosure, there isprovided a medicament delivery device comprising:

-   -   a housing configured to receive a cartridge containing a        medicament;    -   an injection needle having a proximal end and a distal end;    -   an injection needle holder to which the injection needle is        fixed, the injection needle holder being moveable relative to        the housing between a rest position and a use position; and    -   an injection needle cap detachably connected to the injection        needle holder and enclosing the proximal end of the injection        needle. The medicament delivery device is configured such that,        when the cartridge is received in the housing, pushing the        injection needle cap towards the cartridge causes the injection        needle holder to move from the rest position in which the distal        end of the injection needle is spaced from the cartridge towards        the use position in which the distal end of the injection needle        can engage the cartridge.

The medicament delivery device may comprise a locking mechanism forpreventing the injection needle holder from moving back towards the restposition when the injection needle holder is in the use position.

The locking mechanism may comprise a first locking element provided onthe housing and a second locking element provided on the injectionneedle holder. When the injection needle holder is in the use position,the first locking element and the second locking element may cooperateto prevent the injection needle holder to move back towards the restposition.

The medicament delivery device may comprise a retaining mechanism forpreventing the injection needle holder from being removed from thehousing.

The medicament delivery device may comprise a plurality of armsprojecting from the injection needle holder and extending around thedistal end of the injection needle. When the cartridge is received inthe housing, the arms may be configured to slide along the cartridgewhen the injection needle holder moves from the rest position towardsthe use position.

The retaining mechanism may comprise a retaining element provided on atleast one of the arms. When the cartridge is received in the housing andwhen the injection needle holder is in the rest position, the retainingelement may cooperate with the cartridge to prevent the injection needleholder from being removed from the housing.

At least one of the arms may comprise a fastening element. When thecartridge is received in the housing and when the injection needleholder is in the use position, the fastening element may cooperate withthe cartridge to prevent the injection needle holder from moving towardsthe rest position.

The arms may be made with a flexible material.

In the rest position of the injection needle holder, the arms may beconnected to each other by means of a breakable material.

When the injection needle holder moves from the rest position towardsthe use position, the arms may move away from each other such that thebreakable material breaks.

The breakable material may be made of foil.

The medicament delivery device may comprise a first arm and a secondarm. The first and second arms may face each other and may extend aroundthe distal end of the injection needle.

The medicament delivery device may comprise an outer sleeve mounted onthe housing. The injection needle cap may be connected to the outersleeve such that, when the injection needle holder is in the useposition, detaching the injection needle cap from the injection needleholder causes disengagement of the outer sleeve from the housing.

The medicament delivery device may comprise a cartridge of medicament.The cartridge may be retained to the housing. In the rest position, theinjection needle holder may be engaged with the cartridge.

In the rest position, the distal end of the injection needle may besealed by the arms, the breakable material and the cartridge.

The terms “drug” or “medicament” which are used interchangeably herein,mean a pharmaceutical formulation that includes at least onepharmaceutically active compound.

The term “drug delivery device” shall be understood to encompass anytype of device, system or apparatus designed to immediately dispense adrug to a human or non-human body (veterinary applications are clearlycontemplated by the present disclosure). By “immediately dispense” ismeant an absence of any necessary intermediate manipulation of the drugby a user between discharge of the drug from the drug delivery deviceand administration to the human or non-human body. Without limitation,typical examples of drug delivery devices may be found in injectiondevices, inhalers, and stomach tube feeding systems. Again withoutlimitation, exemplary injection devices may include, e.g., syringes,autoinjectors, injection pen devices and spinal injection systems.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the present disclosure are described withreference to the accompanying drawings, in which:

FIGS. 1A and 1B show schematic side views of a medicament deliverydevice which may include embodiments of the present disclosure;

FIG. 2A shows a cross-sectional view of a part of a medicament deliverydevice according to an embodiment of the present disclosure, the needlebeing in a rest position;

FIG. 2B shows a cross-sectional view of a part of the medicamentdelivery device of FIG. 2A taken along the line A-A shown in FIG. 2A;

FIG. 3 shows a cross-sectional view of the part of the medicamentdelivery device of FIG. 2A, the needle being in a use position;

FIGS. 4A and 4B show perspective views of the needle cap and the needleholder of the medicament delivery device of FIG. 2A; and

FIGS. 5A to 5C show general principle perspective views of themedicament delivery device of FIG. 2A.

DETAILED DESCRIPTION

Embodiments of the present disclosure provide a mechanism for insertingthe injection needle of a medicament delivery device such as anauto-injector into a medicament cartridge containing the medicament tobe injected. Providing such a mechanism allows the medicament cartridgeto be sealed until such time as the user wishes to commence theinjection. Providing an automated mechanism for inserting the needleinto the medicament cartridge also reduces the amount of handling of theneedle by the user prior to the injection. Indeed, in embodiments of thedisclosure, the user does not need to touch the needle during the stepsof inserting the needle into the medicament cartridge and subsequentlyactuating the injection of the medicament.

The terms “proximal” and “distal” herein respectively refer to asrelatively closer to the patient and relatively further away from thepatient.

A drug delivery device, as described herein, may be configured to injecta medicament into a patient. For example, delivery could besub-cutaneous, intra-muscular, or intravenous. Such a device could beoperated by a patient or care-giver, such as a nurse or physician, andcan include various types of safety syringe, pen-injector, orauto-injector. The device can include a cartridge-based system thatrequires piercing a sealed ampule before use. Volumes of medicamentdelivered with these various devices can range from about 0.5 ml toabout 2 ml. Yet another device can include a large volume device (“LVD”)or patch pump, configured to adhere to a patient's skin for a period oftime (e.g., about 5, 15, 30, 60, or 120 minutes) to deliver a “large”volume of medicament (typically about 2 ml to about 10 ml).

In combination with a specific medicament, the presently describeddevices may also be customized in order to operate within requiredspecifications. For example, the device may be customized to inject amedicament within a certain time period (e.g., about 3 to about 20seconds for auto-injectors, and about 10 minutes to about 60 minutes foran LVD). Other specifications can include a low or minimal level ofdiscomfort, or to certain conditions related to human factors,shelf-life, expiry, biocompatibility, environmental considerations, etc.Such variations can arise due to various factors, such as, for example,a drug ranging in viscosity from about 3 cP to about 50 cP.Consequently, a drug delivery device will often include a hollow needleranging from about 25 to about 31 Gauge in size. Common sizes are 27 and29 Gauge.

The delivery devices described herein can also include one or moreautomated functions. For example, one or more of needle insertion,medicament injection, and needle retraction can be automated. Energy forone or more automation steps can be provided by one or more energysources. Energy sources can include, for example, mechanical, pneumatic,chemical, or electrical energy. For example, mechanical energy sourcescan include springs, levers, elastomers, or other mechanical mechanismsto store or release energy. One or more energy sources can be combinedinto a single device. Devices can further include gears, valves, orother mechanisms to convert energy into movement of one or morecomponents of a device.

The one or more automated functions of an auto-injector may each beactivated via an activation mechanism. Such an activation mechanism caninclude one or more of a button, a lever, a needle sleeve, or otheractivation component. Activation of an automated function may be aone-step or multi-step process. That is, a user may need to activate oneor more activation components in order to cause the automated function.For example, in a one-step process, a user may depress a needle sleeveagainst their body in order to cause injection of a medicament. Otherdevices may require a multi-step activation of an automated function.For example, a user may be required to depress a button and retract aneedle shield in order to cause injection.

In addition, activation of one automated function may activate one ormore subsequent automated functions, thereby forming an activationsequence. For example, activation of a first automated function mayactivate at least two of needle insertion, medicament injection, andneedle retraction. Some devices may also require a specific sequence ofsteps to cause the one or more automated functions to occur. Otherdevices may operate with a sequence of independent steps.

Some delivery devices can include one or more functions of a safetysyringe, pen-injector, or auto-injector. For example, a delivery devicecould include a mechanical energy source configured to automaticallyinject a medicament (as typically found in an auto-injector) and a dosesetting mechanism (as typically found in a pen-injector).

According to some embodiments of the present disclosure, an exemplarydrug delivery device 10 is shown in FIGS. 1A and 1B. Device 10, asdescribed above, is configured to inject a medicament into a patient'sbody. Device 10 includes a housing 11 which typically contains areservoir containing the medicament to be injected, e.g., a cartridge12, and the components required to facilitate one or more steps of thedelivery process. Device 10 can also include a cap assembly 14 that canbe detachably mounted to the housing 11. Typically a user must removecap 14 from housing 11 before device 10 can be operated.

As shown, housing 11 is substantially cylindrical and has asubstantially constant diameter along the longitudinal axis X. Thehousing 11 has a proximal region 16 and a distal region 21.

The term “proximal” refers to a location that is relatively closer to asite of injection, and the term “distal” refers to a location that isrelatively further away from the injection site.

Device 10 can also include a needle sleeve or inner sleeve 15 coupled tohousing 11 to permit movement of sleeve 15 relative to housing 11. Forexample, sleeve 15 can move in a longitudinal direction parallel tolongitudinal axis X. Specifically, movement of sleeve 15 in a distaldirection can permit a needle 13 to extend from proximal region 16 ofhousing 11.

Insertion of needle 13 can occur via several mechanisms. For example,needle 13 may be fixedly located relative to housing 11 and initially belocated within an extended needle sleeve 15. Distal movement of sleeve15 by placing a proximal end of sleeve 15 against a patient's body andmoving housing 11 in a proximal direction will uncover the proximal endof needle 13. Such relative movement allows the proximal end of needle13 to extend into the patient's body. Such insertion is termed “manual”insertion as needle 13 is manually inserted via the patient's manualmovement of housing 11 relative to sleeve 15.

Another form of insertion is “automated,” whereby needle 13 movesrelative to housing 11. Such insertion can be triggered by movement ofsleeve 15 or by another form of activation, such as, for example, abutton 22. As shown in FIGS. 1A and 1B, button 22 is located at a distalend of housing 11. However, in other embodiments, button 22 could belocated on a side of housing 11.

Other manual or automated features can include drug injection or needleretraction, or both. Injection is the process by which a bung or piston34 is moved from a distal location within the cartridge 12 to a moreproximal location within the cartridge in order to force a medicamentfrom the cartridge 12 through needle 13. In some embodiments, a drivespring (not shown) is under compression before device 10 is activated. Adistal end of the drive spring can be fixed within distal region 21 ofhousing 11, and a proximal end of the drive spring can be configured toapply a compressive force to a distal surface of piston 34. Followingactivation, at least part of the energy stored in the drive spring canbe applied to the distal surface of piston 34. This compressive forcecan act on piston 34 to move it in a proximal direction. Such proximalmovement acts to compress the liquid medicament within the cartridge 12,forcing it out of needle 13.

Following injection, needle 13 can be retracted within sleeve 15 orhousing 11. Retraction can occur when sleeve 15 moves proximally as auser removes device 10 from a patient's body. This can occur as needle13 remains fixedly located relative to housing 11. Once a proximal endof sleeve 15 has moved pasta proximal end of needle 13, and needle 13 iscovered, sleeve 15 can be locked. Such locking can include locking anydistal movement of sleeve 15 relative to housing 11.

Another form of needle retraction can occur if needle 13 is movedrelative to housing 11. Such movement can occur if the cartridge 12within housing 11 is moved in a distal direction relative to housing 11.This distal movement can be achieved by using a retraction spring (notshown), located in proximal region 16. A compressed retraction spring,when activated, can supply sufficient force to the cartridge 12 to moveit in a distal direction. Following sufficient retraction, any relativemovement between needle 13 and housing 11 can be locked with a lockingmechanism. In addition, button 22 or other components of device 10 canbe locked as required.

As shown in FIG. 2A, the housing 11 includes a first protruding part 23and a second protruding part 24. The first and second protruding parts23, 24 project inwardly from the sidewall 18 of the housing 11. Thefirst protruding part 23 forms a cartridge holder 25 for securing thecartridge 12 in the housing 11. The first protruding part 23 defines afirst passage 26 through which a plunger 20 can move. A circumferentialstop 27 extends inwardly from the first protruding part 23. The secondprotruding part 24 forms a second passage 28 axially aligned with thefirst passage 26. The second protruding part 24 is shown in more detailin FIG. 2B. The second protruding part 24 includes a first clip 29 and asecond clip 30 distributed around the second passage 28 such that thefirst and second clips 29, 30 face each other.

The cartridge 12 is in the form of a tubular hollow body 31 which storesthe liquid medicament to be injected to the patient's body. The hollowbody 31 comprises a proximal portion 32 and a distal portion 33. Thedistal portion 33 is fitted within the first passage 26 via a transitionfit and abuts against the circumferential stop 27. The hollow body 31contains the piston or stopper 34 and a crimp cap 35 between which themedicament is contained. The stopper 34 has substantially the same crosssection as the hollow body 31 so that the stopper 34 forms a seal withthe hollow body 31. Prior injection, the stopper 34 is located in thedistal portion 33 of the hollow body 31. During injection, the stopper34 is moved by the plunger 20 towards the proximal portion 32 to deliverthe medicament. The crimp cap 35 is secured to the proximal portion 32of the hollow body 31 and comprises a sealing membrane 36 for sealingthe proximal portion 32 of the hollow body 31.

The inner sleeve 15 is generally tubular and fits inside the housing 11.The inner sleeve or needle cover 15 is slidable relative to the housing11 between a deployed position in which the inner sleeve 15 protrudesfrom the proximal region 16 of the housing 11 and a retracted positionin which the inner sleeve 15 is retracted within the housing 11. In thedeployed position, the inner sleeve 15 surrounds the needle 13 toprevent unwanted exposure of the needle 13. In the retracted position,the inner sleeve 15 entirely locates within the housing 11 such that theneedle 13 is exposed. Rotation of the inner sleeve 15 relative to thehousing 11 is prevented by a splined arrangement (not shown).

The injection needle 13 is in the form of a hollow needle 13 comprisinga proximal end 37, a distal end 38, and an intermediate section 39joining the proximal end 37 and the distal end 38 together.

The needle 13 is fixed to a needle holder 40 which is configured to movefrom a rest position towards a use position. In the rest position, theneedle holder 40 is positioned relative to the cartridge 12 such thatthe distal end 38 of the needle 13 is spaced from the cartridge 12 andtherefore cannot engage the cartridge 12. In the use position, theneedle holder 40 is positioned relative to the cartridge 12 such thatthe distal end 38 of the needle 13 is inserted in the cartridge 12.

The needle holder 40 comprises a needle supporting portion 41 having aneedle hub 41 a to which the intermediate section 39 of the needle 13 issecured. The needle supporting portion 41 comprises a first projection42 and second projection 43 configured to abut respectively the firstand second clips 29, 30 when the needle 13 is in the use position. Thefirst and second clips 29, 30 along with the first and secondprojections 42, 43 form a locking mechanism configured to prevent theneedle holder 40 from moving back towards the rest position when theneedle holder 40 has reached the use position. In particular, the firstand second clips 29, 30 and the first and second projections 42, 43 actas a ratchet mechanism which allows the needle holder 40 to move in afirst axial direction towards the use position while preventing theneedle holder 40 to move in a second axial direction opposed to thefirst axial direction once the needle holder 40 has reached the useposition.

A first arm 44 and a second arm 45 project from the needle supportingportion 41. The needle 13 is positioned in the needle holder 40 suchthat the distal end 38 of the needle 13 extends between the first andsecond arms 44, 45. The first and second arms 44, 45 are made with aflexible material. In the rest position, the first and second arms 44,45 extend substantially parallel to each other. The first and secondarms 44, 45 each have a free end 46 opposite the needle supportingportion 41. A retaining element 47 in the form of a lip 47 locates ateach free end 46. Each lip 47 projects inwardly from each correspondingfree end 46. The first and second arms 44, 45 each comprises a fasteningelement 48 in the form of a protrusion 48 respectively protruding froman inner surface 49 of the first arm 44 and an inner surface 50 of thesecond arm 45. The protrusions 48 are located at a distance from theneedle supporting portion 41 which is such that the crimp cap 35 canlocate between the needle supporting portion 41 and the protrusions 48when the needle holder 40 is in the use position.

The first and second arms 44, 45 are configured to slide along thecartridge 12 when the needle holder 40 moves from the rest positiontowards the use position. When the needle holder 40 is in the restposition, the lips 47 abut against the crimp cap 35 so that the needleholder 40 is prevented from being removed from the housing 11 (FIG. 2A).In the use position, the protrusions 48 abut against the crimp cap 35 sothat the needle holder 40 is fixed relative to the cartridge 12. Theprotrusions 48 also act as an additional locking feature for preventingthe needle holder 40 to move back towards the rest position.

The needle holder 40 is shown in greater detail in FIGS. 4A and 4B. Inthe rest position, the first and second arms 44, 45 are connected toeach other by means of a breakable material such as a foil 51 having afrangible line 52 (FIG. 4A). In the use position, the foil 51 is brokenalong the frangible line 52 such that the first and second arms 44, 45are separated (FIG. 4B). It will be noted that other kinds of breakablematerial could be used.

In the rest position, the distal end 38 of the needle 13 is sealed bythe first and second arms 44, 45, the foil 51 and the crimp cap 35 ofthe cartridge 12 so that the distal end 38 is sealed againstenvironmental conditions and so that contamination of the distal end 38is prevented. When the needle holder 40 moves towards the use position,the first and second arms 44, 45 slide over the cartridge 12 such thatthe first and second arms 44, 45 move away from each other, which breaksthe foil 51 along the frangible line 52 and unseal the distal end 38 ofthe needle 13.

The cap assembly 14 comprises an outer sleeve 53 (shown in FIGS. 5A to5C) and a needle cap 54. The needle cap 54 encloses the proximal end 37of the needle 13 to protect the proximal end 37 when the device 10 isnot in use. The needle cap 54 seals the proximal end 37 againstenvironmental conditions and prevents contamination of the proximal end37. The needle cap 54 is substantially tubular. The diameter of theneedle cap 54 is such that an internal surface of the needle cap 54tightly abuts the needle hub 41 a to securely locate the needle cap 54thereon. The outer sleeve 53 is mounted on the housing 11 and extendsabout the circumference of the housing 11. The outer sleeve 53 isconnected to the needle cap 54 such that, when the needle holder 40 isin the use position, detaching the needle cap 54 from the needle holder40 causes disengagement of the outer sleeve 53 from the housing. Theneedle cap 54 is mounted to the needle holder 40 such that pushing theneedle cap 54 towards the cartridge 12 causes the needle holder 40 tomove from the rest position towards the use position.

The operation of the medicament injection device 10 in accordance withthe present disclosure will now be described with reference to FIGS. 5Ato 5C which illustrate general principle views of the medicamentinjection device 10 according to the disclosure.

Initially, the distal portion 33 of the cartridge 12 is fitted withinthe first passage 26 and abuts against the circumferential stop 27. Thecap assembly 14 is mounted to the housing 11 (FIG. 5A). The needle cap54 is mounted to the needle hub 41 a so that the proximal end 37 of theneedle 13 is enclosed within the needle cap 54. The needle holder 40 isin the rest position, i.e. the distal end 38 of the needle 13 is spacedfrom the cartridge 12. The distal end 38 of the needle 13 is sealed bythe first and second arms 44, 45, the foil 51 and the crimp cap 35 ofthe cartridge 12. The lips 47 abut against the crimp cap 35 so that theneedle holder 40 is prevented from being removed from the housing 11(FIG. 2A).

In use of the device 10, the needle cap 54 is pushed towards thecartridge 12, as shown by the arrow A in FIG. 5B, such that the needleholder 40 moves from the rest position towards the use position. As theneedle holder 40 moves towards the use position, the first and secondarms 44, 45 slide over the cartridge 12 towards the distal portion 33 ofthe cartridge 12 until the first and second projections 42, 43 movebeyond the first and second clips 29, 30 and respectively abut againstthe first and second clips 29, 30. The first and second arms 44, 45 moveaway from each other such that the foil 51 breaks along the frangibleline 52 and unseals the distal end 38 of the needle 13. Simultaneously,the distal end 38 of the needle 13 moves closer to the proximal portion32 of the cartridge 12 and pierces the sealing membrane 36 of the crimpcap 35. Once the needle holder 40 has reached the use position, thecrimp cap 35 locates between the needle supporting portion 41 and theprotrusions 48. The protrusions 48 abut against the crimp cap 35 so thatthe needle holder 40 is fixed relative to the cartridge 12.

Then, the cap assembly 14 is pulled away from the housing 11, as shownby the arrow B in FIG. 5C. As the cap assembly 14 is pulled away fromthe housing 11, the needle cap 54 detaches from the needle hub 41 a toexpose the proximal end 37 of the needle 13. The device 10 is then readyfor injection. To perform an injection, the sleeve 15 is retracted intothe housing 11 to uncover the proximal end 37 of the needle 13. Then,the driving mechanism actuates the plunger 20 which moves the stopper 34towards the proximal portion 32 of the cartridge 12 such that medicamentis delivered through the needle 13. After the injection, the sleeve 15extends again in the deployed position and covers the proximal end 37 ofthe needle 13 for safe disposal of the device 10.

It will be appreciated that various changes and modifications can bemade to the medicament injection device described herein withoutdeparting from the scope of the present invention, as set out in theappended claims.

For example, the needle cap 54 is described in the illustratedembodiment as tightly abutting the needle hub 41 a so that the needlecap 54 securely locates on the needle hub 41 a. However, the disclosureis not intended to be limited to this particular type of connectionbetween the needle cap 54 and the needle holder 40. The needle cap 54can be connected to the needle holder 40 by means of a breakable bond.The needle cap 54 can be glued to the needle holder 40, the glue beingconfigured such that the needle cap 34 is not permanently adhered to theneedle holder 40 and can be removed therefrom. In a further variant, theneedle cap 54 and the needle holder 40 can be formed integrally and havea line of weakness extending between the needle cap 54 and the needleholder 40. The line of weakness can, for example, be in the form of aplurality of breakable tabs. In a further variant, the needle cap 54 canbe removably mounted to the needle holder 40 by means of a transitionfit.

The terms “drug” or “medicament” are used synonymously herein anddescribe a pharmaceutical formulation containing one or more activepharmaceutical ingredients or pharmaceutically acceptable salts orsolvates thereof, and optionally a pharmaceutically acceptable carrier.An active pharmaceutical ingredient (“API”), in the broadest terms, is achemical structure that has a biological effect on humans or animals. Inpharmacology, a drug or medicament is used in the treatment, cure,prevention, or diagnosis of disease or used to otherwise enhancephysical or mental well-being. A drug or medicament may be used for alimited duration, or on a regular basis for chronic disorders.

As described below, a drug or medicament can include at least one API,or combinations thereof, in various types of formulations, for thetreatment of one or more diseases. Examples of API may include smallmolecules having a molecular weight of 500 Da or less; polypeptides,peptides and proteins (e.g., hormones, growth factors, antibodies,antibody fragments, and enzymes); carbohydrates and polysaccharides; andnucleic acids, double or single stranded DNA (including naked and cDNA),RNA, antisense nucleic acids such as antisense DNA and RNA, smallinterfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleicacids may be incorporated into molecular delivery systems such asvectors, plasmids, or liposomes. Mixtures of one or more drugs are alsocontemplated.

The term “drug delivery device” shall encompass any type of device orsystem configured to dispense a drug or medicament into a human oranimal body. Without limitation, a drug delivery device may be aninjection device (e.g., syringe, pen injector, auto injector,large-volume device, pump, perfusion system, or other device configuredfor intraocular, subcutaneous, intramuscular, or intravasculardelivery), skin patch (e.g., osmotic, chemical, micro-needle), inhaler(e.g., nasal or pulmonary), an implantable device (e.g., drug- orAPI-coated stent, capsule), or a feeding system for thegastro-intestinal tract. The presently described drugs may beparticularly useful with injection devices that include a needle, e.g.,a hypodermic needle for example having a Gauge number of 24 or higher.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other solidor flexible vessel configured to provide a suitable chamber for storage(e.g., short- or long-term storage) of one or more drugs. For example,in some instances, the chamber may be designed to store a drug for atleast one day (e.g., 1 to at least 30 days). In some instances, thechamber may be designed to store a drug for about 1 month to about 2years. Storage may occur at room temperature (e.g., about 20° C.), orrefrigerated temperatures (e.g., from about −4° C. to about 4° C.). Insome instances, the drug container may be or may include a dual-chambercartridge configured to store two or more components of thepharmaceutical formulation to-be-administered (e.g., an API and adiluent, or two different drugs) separately, one in each chamber. Insuch instances, the two chambers of the dual-chamber cartridge may beconfigured to allow mixing between the two or more components prior toand/or during dispensing into the human or animal body. For example, thetwo chambers may be configured such that they are in fluid communicationwith each other (e.g., by way of a conduit between the two chambers) andallow mixing of the two components when desired by a user prior todispensing. Alternatively or in addition, the two chambers may beconfigured to allow mixing as the components are being dispensed intothe human or animal body.

The drugs or medicaments contained in the drug delivery devices asdescribed herein can be used for the treatment and/or prophylaxis ofmany different types of medical disorders. Examples of disordersinclude, e.g., diabetes mellitus or complications associated withdiabetes mellitus such as diabetic retinopathy, thromboembolismdisorders such as deep vein or pulmonary thromboembolism. Furtherexamples of disorders are acute coronary syndrome (ACS), angina,myocardial infarction, cancer, macular degeneration, inflammation, hayfever, atherosclerosis and/or rheumatoid arthritis. Examples of APIs anddrugs are those as described in handbooks such as Rote Liste 2014, forexample, without limitation, main groups 12 (anti-diabetic drugs) or 86(oncology drugs), and Merck Index, 15th edition.

Examples of APIs for the treatment and/or prophylaxis of type 1 or type2 diabetes mellitus or complications associated with type 1 or type 2diabetes mellitus include an insulin, e.g., human insulin, or a humaninsulin analogue or derivative, a glucagon-like peptide (GLP-1), GLP-1analogues or GLP-1 receptor agonists, or an analogue or derivativethereof, a dipeptidyl peptidase-4 (DPP4) inhibitor, or apharmaceutically acceptable salt or solvate thereof, or any mixturethereof. As used herein, the terms “analogue” and “derivative” refer toany substance which is sufficiently structurally similar to the originalsubstance so as to have substantially similar functionality or activity(e.g., therapeutic effectiveness). In particular, the term “analogue”refers to a polypeptide which has a molecular structure which formallycan be derived from the structure of a naturally occurring peptide, forexample that of human insulin, by deleting and/or exchanging at leastone amino acid residue occurring in the naturally occurring peptideand/or by adding at least one amino acid residue. The added and/orexchanged amino acid residue can either be codable amino acid residuesor other naturally occurring residues or purely synthetic amino acidresidues. Insulin analogues are also referred to as “insulin receptorligands”. In particular, the term “derivative” refers to a polypeptidewhich has a molecular structure which formally can be derived from thestructure of a naturally occurring peptide, for example that of humaninsulin, in which one or more organic substituent (e.g. a fatty acid) isbound to one or more of the amino acids. Optionally, one or more aminoacids occurring in the naturally occurring peptide may have been deletedand/or replaced by other amino acids, including non-codeable aminoacids, or amino acids, including non-codeable, have been added to thenaturally occurring peptide.

Examples of insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin (insulinglulisine); Lys(B28), Pro(B29) human insulin (insulin lispro); Asp(B28)human insulin (insulin aspart); human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Examples of insulin derivatives are, for example,B29-N-myristoyl-des(B30) human insulin, Lys(B29)(N-tetradecanoyl)-des(B30) human insulin (insulin detemir, Levemir®);B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl human insulin;B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 humaninsulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N—(N-palmitoyl-gamma-glutamyl)-des(B30) humaninsulin, B29-N-omega-carboxypentadecanoyl-gamma-L-glutamyl-des(B30)human insulin (insulin degludec, Tresiba®);B29-N—(N-lithocholyl-gamma-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyhepta¬decanoyl) human insulin.

Examples of GLP-1, GLP-1 analogues and GLP-1 receptor agonists are, forexample, Lixisenatide (Lyxumia®, Exenatide (Exendin-4, Byetta®,Bydureon®, a 39 amino acid peptide which is produced by the salivaryglands of the Gila monster), Liraglutide (Victoza®), Semaglutide,Taspoglutide, Albiglutide (Syncria®), Dulaglutide (Trulicity®),rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlenatide/HM-11260C, CM-3,GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen,Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, MAR-701,MAR709, ZP-2929, ZP-3022, TT-401, BHM-034. MOD-6030, CAM-2036, DA-15864,ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten.

An example of an oligonucleotide is, for example: mipomersen sodium(Kynamro®), a cholesterol-reducing antisense therapeutic for thetreatment of familial hypercholesterolemia. Examples of DPP4 inhibitorsare Vildagliptin, Sitagliptin, Denagliptin, Saxagliptin, Berberine.

Examples of hormones include hypophysis hormones or hypothalamushormones or regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Examples of polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20 (Synvisc®), a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)2 fragments, which retain the ability to bind antigens. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix a complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region. The term antibody also includes anantigen-binding molecule based on tetravalent bispecific tandemimmunoglobulins (TBTI) and/or a dual variable region antibody-likebinding protein having cross-over binding region orientation (CODV).

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentinvention include, for example, Fab fragments, F(ab′)2 fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific,tetraspecific and multispecific antibodies (e.g., diabodies, triabodies,tetrabodies), monovalent or multivalent antibody fragments such asbivalent, trivalent, tetravalent and multivalent antibodies, minibodies,chelating recombinant antibodies, tribodies or bibodies, intrabodies,nanobodies, small modular immunopharmaceuticals (SMIP), binding-domainimmunoglobulin fusion proteins, camelized antibodies, and VHH containingantibodies. Additional examples of antigen-binding antibody fragmentsare known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Examples of antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

Pharmaceutically acceptable salts of any API described herein are alsocontemplated for use in a drug or medicament in a drug delivery device.Pharmaceutically acceptable salts are for example acid addition saltsand basic salts.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the APIs, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentinvention, which encompass such modifications and any and allequivalents thereof.

1. A method comprising: pushing an injection needle cap of a medicamentdelivery device toward a cartridge such that a holder for an injectionneedle is moved distally from a rest position and such that a distal endof an injection needle engages the cartridge; and pulling the injectionneedle cap away from the cartridge to expose a proximal end of theinjection needle of the medicament delivery device for injection.
 2. Themethod of claim 1, wherein pushing the injection needle cap towards thecartridge comprises causing the holder for the injection needle to movefrom the rest position in which the distal end of the injection needleis spaced from the cartridge towards a use position in which the distalend of the injection needle engages the cartridge.
 3. The method ofclaim 1, wherein pushing the injection needle cap toward the cartridgecomprises causing a plurality of arms of the holder to move away fromeach other such that a breakable material connecting the plurality ofarms breaks.
 4. The method of claim 3, wherein the breakable materialbreaks along a frangible line provided in the breakable material.
 5. Themethod of claim 3, wherein the breakable material comprises a foil. 6.The method of claim 3, wherein in the rest position, before pushing theinjection needle cap toward the cartridge, the distal end of theinjection needle is sealed by the plurality of arms, the breakablematerial, and the cartridge.
 7. The method of claim 1, wherein pushingthe injection needle cap toward the cartridge comprises causing aplurality of arms of the holder to slide along the cartridge.
 8. Themethod of claim 7, wherein in the rest position, before pushing theinjection needle cap toward the cartridge, the plurality of arms projectfrom the holder and extend around the distal end of the injectionneedle.
 9. The method of claim 7, wherein the plurality of arms comprisea first arm and a second arm, wherein the first and second arms faceeach other and extend around the distal end of the injection needle. 10.The method of claim 7, wherein the plurality of arms comprise a flexiblematerial.
 11. The method of claim 1, wherein pushing the injectionneedle cap toward the cartridge comprises causing a locking mechanism ofthe medicament delivery device to prevent the holder from moving backtoward the rest position.
 12. The method of claim 11, wherein thelocking mechanism allows the holder to move in a first axial directiontowards the cartridge and to a use position, whilst preventing theholder from moving in a second axial direction opposed to the firstaxial direction once the holder has reached the use position.
 13. Themethod of claim 12, wherein the locking mechanism comprises a firstlocking element provided on a housing of the medicament delivery deviceand a second locking element provided on the holder, wherein, when theholder is in the use position, the first locking element and the secondlocking element cooperate to prevent the holder from moving back towardsthe rest position.
 14. The method of claim 12, wherein the lockingmechanism comprises a first locking element provided on a housing of amedicament delivery device and a second locking element provided on theholder, wherein pushing the injection needle cap toward the cartridgecomprises causing the second locking element to move beyond the firstlocking element and abut against the second locking element, to preventthe holder from moving back towards the rest position.
 15. The method ofclaim 12, wherein the locking mechanism comprises at least oneprojection provided on the holder and at least one clip provided on ahousing of a medicament delivery device, wherein pushing the injectionneedle cap toward the cartridge comprises causing the projection to movebeyond the clip and abut against the clip, to prevent the holder frommoving back towards the rest position.
 16. The method of claim 1,wherein in the rest position, the holder is prevented from being removedfrom a housing of the medicament delivery device by a retainingmechanism.
 17. The method of claim 1, wherein before pushing theinjection needle cap toward the cartridge, a retaining element providedon at least one of a plurality of arms of the holder cooperates with thecartridge to prevent the holder from being removed from a housing of themedicament delivery device.
 18. The method of claim 1, wherein pushingthe injection needle cap towards the cartridge comprises causing afastening element provided on at least one of a plurality of arms of theholder to cooperate with the cartridge, to prevent the holder frommoving towards the rest position.
 19. The method of claim 1, whereinpushing the injection needle cap towards the cartridge comprises causinga fastening element provided on at least one of a plurality of arms ofthe holder to cooperate with the cartridge, such that the holder isfixed relative to the cartridge.
 20. The method of claim 1, whereinpulling the injection needle cap away from the cartridge comprisesdetaching the injection needle cap from the holder to causedisengagement of an outer sleeve of the medicament delivery device froma housing of the medicament delivery device.